This interdisciplinary research proposal for molecular target assessment for angiogenesis and anti-angiogenic therapy will require a great deal of histopathologic studies. One of the main objectives of this overall proposal is to determine if non-invasive methods of evaluating the effect of anti-angiogenic therapy correlates with immunohistopathologic findings. In anti-angiogenic clinical trials, we have proposed harvesting tissue prior to anti-angiogenic therapy and after initiation of anti-angiogenic therapy. Non-invasive imaging techniques will assess the effect of these agents on angiogenic activity and tumor perfusion. We will correlate these non-invasive findings with immunohistopathologic findings within tumor specimens. Therefore, the Core Immunohistopathologic Laboratory is essential for examining tumor vascularity. In addition, all of the research projects will involve the use of immunohistopathology to assess the effects of anti-angiogenic therapy by various mechanisms (including inhibition of growth factor receptor activity, angiogenic factor receptor activity, or vascular targeting peptides). Furthermore, other studies are proposed examining the basic biology of alterations in angiogenic factor expression, and its effect on angiogenesis in mouse models of tumor growth. The Immunohistopathology Laboratory Core will serve as the physical, intellectual, and imaging center for all immunopathologic studies done. This includes Research Projects 1, 2,3,4, as well as Developmental Projects 1, 2, and 3. This laboratory will function to section tissues, prepare slides, provide reagents and equipment for immunohistochemical analysis, as well as in situ hybridization analyses, and provide microscopic and computer imaging systems for evaluation and reporting of findings.